We have been using an autotransporter produced by E. coli O157:H7 called EspP as a model protein to study autotransporter biogenesis. We showed several years ago that after the EspP passenger domain is translocated across the OM it is released into the extracellular milieu through an autocatalytic cleavage reaction that involves the activation of an asparagine residue. In one major line of investigation we have been examining the mechanism by which the EspP passenger domain is translocated across the OM. It was originally proposed that the passenger domain is secreted through a channel formed by the covalently linked beta domain (whence the name autotransporter), but results that we obtained from both biochemical and structural studies appear to be inconsistent with this hypothesis. We found that the insertion of a small linker into the EspP passenger domain effectively creates a translocation intermediate by transiently stalling translocation near the site of the insertion. By using a site-specific photocrosslinking approach we found that residues adjacent to the stall point interact with BamA, a component of a heterooligomeric complex (Bam complex) that catalyzes OM protein assembly, and that residues that are trapped in the periplasm interact with the periplasmic chaperones SurA and Skp. The EspP-BamA interaction was short-lived and could only be detected when passenger domain translocation was stalled. These results support a model in which molecular chaperones prevent misfolding of the passenger domain prior to its secretion and the Bam complex plays a major role in facilitating both the integration of the beta domain into the OM and the translocation of the passenger domain across the OM. We also found that periplasmic chaperones and specific components of the Bam complex interact with the EspP beta domain in a temporally and spatially regulated fashion. While the chaperone Skp initially interacts with the entire beta domain, BamA, BamB and BamD subsequently interact with discrete beta domain regions. BamB and BamD remain bound to the beta domain longer than BamA and therefore appear to function at a later stage of assembly. Our results suggest that the hitherto enigmatic BamB and BamD proteins play a direct role in the membrane integration of autotransporter beta domains and possibly other beta barrel proteins. Interestingly, we also obtained evidence that the completion of beta domain assembly is regulated by an intrinsic checkpoint mechanism that requires the completion of passenger domain secretion. Recently, we have been examining the role of the beta domain in autotransporter biogenesis. It has been known for many years that the beta domain is required for passenger domain secretion, but its exact function has been unclear. We found that two mutations in EspP (G1066A and G1081D) that slightly distort the structure of the beta domain also delay the initiation of passenger domain translocation. Site-specific photocrosslinking experiments revealed that the mutations slow the insertion of the beta domain into the OM, but do not delay the binding of the beta domain to the Bam complex. Our results demonstrate that the beta domain does not simply target the passenger domain to the OM, but promotes translocation when it reaches a specific stage of assembly. Furthermore, our results provide evidence that the Bam complex catalyzes the membrane integration of beta barrel proteins in a multi-step process that can be perturbed by minor structural defects in client proteins.